Sandbox 212: Difference between revisions
Ndeye Coumba (talk | contribs) No edit summary |
Ndeye Coumba (talk | contribs) No edit summary |
||
| Line 44: | Line 44: | ||
There are only slight conformational changes in the enzyme upon carnitine binding.“The only significant conformational difference in the active site between the free enzyme and the carnitine complex is in the side chain of <font color='#90E050'>'''serine454'''</font>, which adopts a different rotamer to have better hydrogen-bonding interactions with the carboxylate of carnitine.” (Cry. Structure) | There are only slight conformational changes in the enzyme upon carnitine binding.“The only significant conformational difference in the active site between the free enzyme and the carnitine complex is in the side chain of <font color='#90E050'>'''serine454'''</font>, which adopts a different rotamer to have better hydrogen-bonding interactions with the carboxylate of carnitine.” (Cry. Structure) | ||
</StructureSection> | </StructureSection> | ||
== | ==Catalytic Mechanism of Carnitine Acyltransferases== | ||
[[Image:Machanism fatty acid transfer.jpg|thumb|700px|left]] | [[Image:Machanism fatty acid transfer.jpg|thumb|700px|left]] | ||
It is assumed that the whole family of carnitine acyltransferases share the same catalytic mechanism, because certain residues in the catalytic side (histidine343, serine554) are conserved throughout the family. | It is assumed that the whole family of carnitine acyltransferases share the same catalytic mechanism, because certain residues in the catalytic side (histidine343, serine554) are conserved throughout the family. | ||
Histidine 343 is probably the most important residue in catalysis. First, it induces optimal substrate binding by forming a hydrogen bond between the hydrogen of the substrate’s reactive group and its side chain. After all substrate attained the right position, the catalytic histidine residue is ready to extract a proton from either the hydroxyl group of carnitine or the thiol group of CoA. Thus the catalytic histidine residue can be considered as a general base in catalysis.Which proton is extracted depends on the direction of the reaction. Acyl- carnitine is formed by extracting a proton from carnitine, whereas acyl-CoA is formed by extracting a proton from CoA. | Histidine 343 is probably the most important residue in catalysis. First, it induces optimal substrate binding by forming a hydrogen bond between the hydrogen of the substrate’s reactive group and its side chain. After all substrate attained the right position, the catalytic histidine residue is ready to extract a proton from either the hydroxyl group of carnitine or the thiol group of CoA. Thus the catalytic histidine residue can be considered as a general base in catalysis.Which proton is extracted depends on the direction of the reaction. Acyl- carnitine is formed by extracting a proton from carnitine, whereas acyl-CoA is formed by extracting a proton from CoA. | ||
The extraction of a hydrogen atom leads to the development of a tetrahedral oxyanion intermediate. This oxyanion is stabilized by the side chain hydroxyl of serine 554 through hydrogen bonding as well as by the positive charge on the trimethylammonium group of carnitine. Since the positive charge of the carnitine substrate is necessary for the carnitine acyltransferase mediated reaction to happen, this catalysis can be described as substrate-assisted catalysis. (1) | |||
The extraction of a hydrogen atom leads to the development of a tetrahedral oxyanion intermediate. This oxyanion is stabilized by the side chain hydroxyl of serine 554 through hydrogen bonding as well as by the positive charge on the trimethylammonium group of carnitine. Since the positive charge of the carnitine substrate is necessary for the carnitine acyltransferase mediated reaction to happen, this catalysis can be described as '''substrate-assisted catalysis'''. (1) | |||
== Regulation == | == Regulation == | ||